Background As many drugs are unavailable for paediatric use, hospital pharmacies are often requested to develop suitable formulations. Clonidine is often used in paediatrics (in severe hypertension or in anaesthetic premedication) but no appropriate formulation is available.
Purpose We developed an oral solution of clonidine dedicated to children and assessed its physicochemical and microbiological stability.
Material and methods Formulation of an oral solution of clonidine hydrochloride was developed using the active pharmaceutical ingredient (API), with the least excipients as possible and suitable for neonates and children. The stability study was led according to the GERPAC-SFPC guidelines. At each time point (D0, D1, D7, D15, D29, D60 and D90), the visual aspect (limpidity) was checked. pH and osmolality were measured (using 2 vials). Clonidine concentration was determined using a stability indicating HPLC-UV-DAD method (a previous forced degradation study under acidic, basic and oxidative conditions allowed the detection of 6 degradation products). Microbiological stability was also tested according to the European Pharmacopoeia monograph after assessing that the culture conditions were adequate to inhibit the effect of the preservative agent, and with the most adapted method. Solutions were stored in brown glass bottles with an oral adapter for up to 3 months under two different conditions: at 2–8°C and at 25°C with 60% residual humidity.
Results The formulated oral solution was composed of API at a concentration of 10 µg/mL and potassium sorbate (0.3%), citric acid, potassium citrate (pH 5) and sodium saccharine (0.025%). On day 29, the mean percentages of the initial clonidine concentrations (±SD) were 92.95±1.28% in the solution stored at 25°C and 97.44±1.21% when stored at 2–8°C. On day 90, the mean values were, respectively, 81.82±0.41% and 93.66±0.71%. The visual aspect did not change. Physical parameters remained stable during the study: pH varied from 4.94 to 5.09 and osmolality from 82 to 92 mOsm/kg under the two conditions tested. Whatever the storage conditions, <1 microorganism/mL was identified (only environmental microorganisms) with no E coli detected.
Conclusion This formulation was stable for at least 3 months when stored at 2–8°C in brown glass bottles and for 1 month when stored at room temperature. The microbiological stability was proven in accordance with the European Pharmacopoeia.
No conflict of interest
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